Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an important protein in a cell death, and plays its role in cell death induced by death receptor or in cell death induced by other cellular stresses. It is known that these cell death signals are induced by binding to a complex with phosphorylation- or deacetylation-dependent RIP1 and mixed lineage kinase domain-like protein (MLKL) and that any protein present in mitochondria is involved in the signals. A regulated mechanism of this signaling system is induced by cell death regulatory proteins to regulate development, as well as cell death and immune responses of lymphocytes, keratinocytes and intestinal epithelial cells. In addition, regulated necrosis plays its roles in degeneration, immunity, and many etiological processes such as infectious disease and ischemic injury.